Botensilimab, Balstilimab and Regorafenib for the Treatment of Patients With Microsatellite Stable Metastatic Colorectal Cancer Who Have Progressed on Prior Chemotherapy

Inclusion Criteria: * Documented informed consent of the participant and/or legally authorized representative. * Assent, when appropriate, will be obtained per institutional guidelines * Age: \>= 18 years * Eastern Cooperative Oncology Group (ECOG) =\< 1 * Life expectancy \>= 3 months * Able to swallow and absorb oral tablets * Histological or cytological confirmed advanced, metastatic, or progressive proficient mismatch repair (pMMR)/MSS adenocarcinoma of colon or rectum * Microsatellite status should be performed per local standard of practice (e.g., immunohistochemistry \[IHC\] and/or polymerase chain reaction \[PCR\], or next-generation sequencing). Only participants with pMMR/MSS mCRC are eligible * Patients should have measurable metastatic disease as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines * Known extended RAS and BRAF status as per local standard of practice. TMB and PD-L1 status will be collected when available but not mandated for enrollment * Patients must have progressed following exposure to all of the following agents: * Fluoropyrimidines (capecitabine or 5-FU) * Irinotecan * Oxaliplatin * Anti-EGFR therapy if RAS and BRAF wild type with left colon primary * Patients must have evidence of progression on or after the last treatment received and within 6 months prior to study enrollment * Patients who were intolerant to prior systemic chemotherapy regimens are eligible if there is documented evidence of clinicall…